EBMT NEWSLETTER | January 2015 | Volume 45 - Issue 3

Important dates
Comparison of Unrelated Cord Blood and Peripheral Blood Stem Cell Transplantation in Adultswith Myelodysplastic Syndrome after Reduced-Intensity Conditioning Regimen: A CollaborativeStudy from Eurocord and Chronic Malignancies Working Party.
Robin M, Ruggeri A, Labopin M, Niederwieser D, Tabrizi R, Sanz G, Bourhis J, van Biezen A, Koenecke C, Blaise D, Tischer J, Craddock C, Maillard N, Mohty M, Russel N, Schetelig J, Finke J, Gluckman E, de Witte TM, Rocha V, Kroger N.
Biol Blood Marrow Transplant. 2014 Dec 19. pii: S1083-8791(14)01384-6. doi: 10.1016/j.bbmt.2014.11.675. [Epub ahead of print]
2014 Dec 19. pii: S1083-8791(14)01384-6. doi: 10.1016/j.bbmt.2014.11.675. [Epub ahead of print]
Results of umbilical cord blood transplants (UCB) using a reduced intensity conditioning (n = 129) have been compared to those of unrelated donors (n = 502) in patients with high-risk myelodisplastic syndrome (MDS) who were considered candidates for allogeneic stem cell transplantation (HSCT) and did not have a HLA-matched sibling donor available.  Multivariate analysis confirmed the superiority of peripheral blood HSCT from unrelated donors over UCB in terms of non-relapse mortality, disease free survival and overall survival; the relative risk of chronic graft versus host disease was similar in both groups of patients. A subset analysis comparing 10/10 and 9/10 HLA-matched donors indicated that the advantage over CB was only seen in the 10/10 group while results between 9/10 unrelated donors and UBC were similar. 10/10 HLA-matched unrelated donors are the preferred source of hematopoietic stem cells for those patients with high-risk MDS who lack a HLA-matched sibling donor.    
Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia.
Brissot E, Labopin M, Beckers MM, Socié G, Rambaldi A, Volin L, Finke J, Lenhoff S, Kröger N, Ossenkoppele GJ, Craddock CF, Yakoub-Agha I, Gürman G, Russell NH, Aljurf M, Potter MN, Nagler A, Ottmann O, Cornelissen JJ, Esteve J,Mohty M.
Haematologica. 2014 Dec 19. pii: haematol.2014.116954. [Epub ahead of print]
Tyrosine-kinase inhibitors have dramatically changed the prognosis of patients diagnosed of Philadelphia chromosome-positive acute lymphoblastic leukemia. Nevertheless, its impact on the long term outcome of these patients when associated to allogeneic stem cell transplantation (HSCT) is still largely unknown. This retrospective analysis of the Acute Leukemia Working Party of the EBMT including 473 de novo Philadelphia chromosome-positive acute lymphoblastic leukemia  in first complete remission who underwent HSCT using a HLA-identical sibling or HLA-matched unrelated donor between 2000 and 2010 largely addresses this point.  Administration of tyrosine-kinase inhibitors before HSCT was associated with a better overall survival and lower relapse incidence. In the post-transplant period, its prophylactic administration was found to be a significant factor for improved leukemia-free survival and overall survival, and a lower relapse incidence.  Prospective studies are needed to verify the potential clinical benefit of the prophylactic administration of tyrorine kinase inhibitors after HSCT to prevent disease relapse.

Managing high-risk CLL during transition to a new treatment era: stem cell transplantation or novel agents?
Dreger P, Schetelig J, Andersen N, Corradini P, van Gelder M, Gribben J, Kimby E, Michallet M, Moreno C, Stilgenbauer S, Montserrat E; European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT).
Blood. 2014 Dec 18;124(26):3841-9. doi: 10.1182/blood-2014-07-586826. Epub 2014 Oct 9.
With the advent of BCRi/BCL2a, next-generation B-cell antibodies, immunomodulators, and possibly additional drug classes in the near future, the current algorithms for chronic lymphocytic leukemia (CLL) management will inevitably change. While allogeneic hematopoietic stem cell transplantation (HSCT) was considered the treatment of choice for patients with high-risk chronic lymphocytic leukemia (HR-CLL; refractory to purine analogs, short response [<24 months] to chemoimmunotherapy, and/or presence of del[17p]/TP53 mutations), nowadays all patients with HR-CLL should be considered for treatment with BCRi/BCL2a if possible within the context of prospective clinical trials. Once a maximum response is achieved, the HSCT option should not be discarded but should be included in the treatment decision process. Conditions potentially favoring immediate transplantation are coincidence of relapsed/refractory HR-CLL with del(17p)/TP53 mutations and/or del(11q), younger age and no significant comorbidities, and availability of a well-matched donor. Factors supporting HSCT deferral are the absence of a relapsed/refractory situation, a relapsed/refractory situation in the absence of del(17p)/TP53 mutations and del(11q), age > 70 years and significant comorbidities, or only a partially matched or mismatched donor available.
The impact of total body irradiation on the outcome of patients with follicular lymphoma treated with autologous stem-cell transplantation in the modern era: a retrospective study of the EBMT Lymphoma Working Party.
El-Najjar I, Boumendil A, Luan JJ, Bouabdallah R, Thomson K, Mohty M, Colombat P, Biron P, Tilly H, Pfreundschuh M, Cordonnier C, Sureda A, Cahn JY, Vernant JP, Gribben J, Cook G, Haynes AP, Ferrant A, Finel H, Montoto S, Dreger P; Lymphoma Working Party of the European Group for Blood and Marrow Transplantation (EBMT).
Ann Oncol. 2014 Nov;25(11):2224-9. doi: 10.1093/annonc/mdu440. Epub 2014 Sep 5.
The role of total body irradiation (TBI) as part of the conditioning regimen in patients with follicular lymphoma being candidates for an autologous stem cell transplantation (ASCT) procedure has been highly debated during many years; while its beneficial therapeutic effect is widely recognized, the higher incidence of long term side effects is of clinical concern. In this retrospective analysis of the Lymphoma Working Party of the EBMT, including 2233 patients with FL treated with ASCT between 1995 and 2007, TBI as part of conditioning regimen was compared with the most frequently used chemotherapy only conditioning regimen, the BEAM protocol. Of note, 47% of the patients included in the analysis were autografted in first complete remission. Interestingly, non-relapse mortality as well as the incidence of secondary malignancies was similar between both groups of patients and as, relapse rate was lower in the TBI treated group, long term disease control was also better with significant differences being achieved in those patients autografted in first complete remission.
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